CCK AND MIDBRAIN DA SYSTEMS--SPECIFICITY OF ACTIONS

八肽缩胆囊素(CCK-8)存在于中脑多巴胺中 含有(DA)的神经元，似乎起到了共递质的作用。这个 这些DA神经元在目前的病因学假说和 治疗几种神经和精神疾病需要 它们的生理和药理反应良好 明白了。近年来，关于受体的研究已有很多。 介导CCK-8对DA神经元影响的亚型，但仍有许多 了解CCK-8在中脑的活动范围和部位。 本申请中提出的研究旨在评估可能的 CCK-8对电生理调制作用的作用部位 麻醉大鼠脑多巴胺能神经元的活动。 中缝背核向中脑的5-羟色胺能传入 影响多巴胺能神经元的电生理活动。在第一个 一组拟议的实验，CCK-8与 刺激中缝背核(和5-羟色胺本身 黑质纹状体和中伏隔DA神经元的活动将被评估。 黑质网状部(SNR)的非DA中间神经元 影响黑质DA神经元的活动，并可能与 本地发布的CCK-8。SNR也是非DA黑质丘脑的来源 和黑质顶盖神经元，它们是锥体外系的重要纽带 马达系统。因此，CCK-8对SNR活性的影响 中间神经元与黑质丘脑和黑质顶盖的逆行识别 神经元将被确定。神经毒素6-OHDA导致退变 并用于制作帕金森氏症的动物模型 疾病。剩余DA神经元的药理反应性 已经被证明有了很大的改变。因为我们之间的亲密关系 在CCK-8和DA之间，可能剩余的响应性 在6-OHDA损毁的大鼠，对CCK-8的DA神经元发生了变化。这样的变化 响应性将对监管具有重要意义 损毁大鼠的DA神经元功能，由此推断，某些疾病 各州。在最后一组实验中，CCK-8对残留的影响 将对6-OHDA损伤大鼠的DA神经元进行测试。经济衰退带来的影响 中脑DA细胞体区DA和CCK-8水平的损害 同时还将确定DA细胞的投射部位。

Cholecystokinin octapeptide (CCK-8) is present within midbrain dopamine (DA)-containing neurons and appears to act as a cotransmitter. The importance of these DA neurons in current hypotheses of the etiology and treatment of several neurological and psychiatric disorders requires that their physiology and their pharmacological responsiveness be well understood. In recent years, much has been learned about the receptor subtypes which mediate the effects of CCK-8 on DA neurons, but much remains to be learned about the scope and sites of CCK-8 actions In the midbrain. The studies proposed in this application are intended to evaluate possible sites of action for modulatory effects of CCK-8 on the electrophysiological activity of DA neurons in anesthetized rats. The serotonergic input to the midbrain from the dorsal raphe nucleus Influences the electrophysiological activity of DA neurons. In the first set of proposed experiments, Interactions of CCK-8 with the effects of dorsal raphe nucleus stimulation (and with serotonin itself on nigrostriatal and mesoaccumbal DA neuronal activity will be evaluated. Non-DA interneurons in the substantia nigra pars reticulata (SNr). Influence the activity of nigral DA neurons and may be accessible to locally released CCK-8. The SNr is also the source of non-DA nigrothalamic and nigrotectal neurons which are important links in the extrapyramidal motor system. Thus, the effects of CCK-8 on the activity of SNr interneurons and antidromically identified nigrothalamic and nigrotectal neurons will be determined. The neurotoxin 6-OHDA causes the degeneration of DA neurons and is used to produce an animal model of Parkinson's disease. The pharmacological responsiveness of the remaining DA neurons has been shown to be greatly altered. Because of the intimate relationship between CCK-8 and DA, it is possible that the responsiveness of remaining DA neurons to CCK-8 is changed in the 6-OHDA-lesioned rat. Such a change In responsiveness would have important implications for the regulation of DA neuronal function in the lesioned rat and, by inference, certain disease states. In the last set of experiments, the effects of CCK-8 on remaining DA neurons in the 6-OHDA-lesioned rat will be tested. The effects of the lesions on DA levels and CCK-8 levels in the midbrain DA cell body region and in DA cell projection sites will also be determined.